Evaluation of Drug-Polymer and Drug-Drug Interaction in Cellulosic Multi-Drug Delivery Matrices.

Multi-drug delivery systems have gained increasing interest from the pharmaceutical industry. Alongside this is the interest in amorphous solid dispersions as an approach to achieve effective oral delivery of compounds with solubility-limited bioavailability. Despite this, there is limited information regarding predicting the behavior of two or more drugs (in amorphous forms) in a polymeric carrier and whether molecular interactions between the compounds, between each compound, and if the polymer have any effect on the physical properties of the system.

Comparative Evaluation of the Powder and Tableting Properties of Regular and Direct Compression Hypromellose from Different Vendors.

Hypromellose, a widely used polymer in the pharmaceutical industry, is available in several grades, depending on the percentage of substitution of the methoxyl and hydroxypropyl groups and molecular weight, and in various functional forms (e.g., suitable for direct compression tableting).

Significant impact of time-of-day variation on metformin pharmacokinetics.

Aims/hypothesis: The objective was to investigate if metformin pharmacokinetics is modulated by time-of-day in humans using empirical and mechanistic pharmacokinetic modelling techniques on a large clinical dataset. This study also aimed to generate and test hypotheses on the underlying mechanisms, including evidence for chronotype-dependent interindividual differences in metformin plasma and efficacy-related tissue concentrations.

Methods: A large clinical dataset consisting of individual metformin plasma and urine measurements was analysed using a newly developed empirical pharmacokinetic model.

Unexpected Stability of a Prodrug to Enzymatic Hydrolysis within a Hydrated HPMC Matrix Tablet.

The uptake of alkaline phosphate present in dissolution medium into a hydrating hydroxypropyl methylcellulose matrix tablet and that its activity was retained therein was demonstrated. This presents a risk to the stability of prodrugs that are substrates of this enzyme such as phosphonooxymethyl derivative prodrugs. It was found that fostemsavir, a phosphonooxymethyl derivative prodrug being developed for the treatment of HIV-1 infection, was unexpectedly resistant to hydrolysis within a hydrated HPMC matrix when subjected to drug release testing in media containing alkaline phosphatase.

A Combined Rheological and Thermomechanical Analysis Approach for the Assessment of Pharmaceutical Polymer Blends.

The viscoelastic nature of polymeric formulations utilised in drug products imparts unique thermomechanical attributes during manufacturing and over the shelf life of the product. Nevertheless, it adds to the challenge of understanding the precise mechanistic behaviour of the product at the microscopic and macroscopic level during each step of the process. Current thermomechanical and rheological characterisation techniques are limited to assessing polymer performance to a single phase and are especially hindered when the polymers are undergoing thermomechanical transitions.

Application of Focus Variation Microscopy and Dissolution Imaging in Understanding the Behaviour of Hydrophilic Matrices.

Hydrophilic matrix systems can be found in a wide range of extended release pharmaceutical formulations. The main principle of these systems is that upon contact with water, the hydrophilic component swells to form a hydrated gel layer which controls drug release. The following work demonstrates an explorative study into the use of dissolution imaging and focus variation microscopy with hydrophilic polymers.

Imaging of the Effect of Alcohol-Containing Media on the Performance of Hypromellose Hydrophilic Matrix Tablets: Comparison of Direct Compression and Regular Grades of Polymer.

As the ingestion of drug products with alcohol could have adverse effects on the release of drugs from dosage forms, it is important to understand the mechanisms underpinning the influence on drug release by evaluating the effect of alcohol-containing media on the behaviour of pharmaceutical excipients. In this work, the effect of hydroalcoholic media containing up to 40% / absolute ethanol was evaluated, employing both the regular (CR) and direct compression grades (DC) of hypromellose. X-ray microtomography (XµT) and magnetic resonance imaging (MRI) were used as complementary techniques in determining the influence of the media composition on the ability of the CR and DC polymers to form and evolve the gel layer that controls drug release.

Characterization of a novel hydroxypropyl methylcellulose (HPMC) direct compression grade excipient for pharmaceutical tablets.

Controlled release tablets are important dosage forms enabling a slower release of the drug and better pharmacokinetics for some drugs and hydrophilic matrix tablets utilizing hydroxypropyl methylcellulose (HPMC) are one of the most common types. One of the main challenges with using HPMC is its poor flow when implemented in a direct compression process or when utilized for continuous manufacturing for which novel grades of direct compression have been developed. In this work, three different direct compression (DC) grades of HPMC (K4M, K15M and K100M) were characterized and compared to their standard grade (CR) counterparts.

Investigation of Within-Tablet Dynamics for Extended Release of a Poorly Soluble Basic Drug from Hydrophilic Matrix Tablets Using ATR-FTIR Imaging.

Hydrophilic matrices are an effective option for oral controlled release but can face challenges in terms of bioavailability and efficacy when used in conjunction with poorly soluble, weakly basic drugs. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) imaging provides dynamic information relating to the location and chemical nature of both the sustained release matrix and the active pharmaceutical ingredient (API) during hydration/dissolution. In this study, we have identified a model system combining itraconazole (IT), a poorly soluble, weakly basic API that has p in the physiological range, and hydroxypropyl methylcellulose, which is a commonly used oral tablet matrix.

Development of a novel method utilising dissolution imaging for the measurement of swelling behaviour in hydrophilic matrices.

A variety of imaging techniques are currently used within the field of pharmaceutics to help understand and determine a wide range of phenomena associated with drug release from hydrophilic matrix tablets. This work for the first time aims at developing an appropriate testing imaging methodology using a surface dissolution imaging instrument (SDI2) for determining the swelling of whole compacts using hypromellose as a model hydrophilic matrix former. The influence of particle morphology (CR and DC grades) and two compressional forces (5 and 15 kN) on the initial swelling behaviour of hypromellose were investigated.

Plasticiser-Free 3D Printed Hydrophilic Matrices: Quantitative 3D Surface Texture, Mechanical, Swelling, Erosion, Drug Release and Pharmacokinetic Studies.

Hydroxypropyl methyl cellulose, HPMC, a hydrophilic polymer, is widely used for the development of extended release hydrophilic matrices and it is also considered as a good contender for the fabrication of 3D printing of matrix tablets. It is often combined with plasticisers to enable extrusion. The aim of the current project was to develop plasticizer-free 3D printed hydrophilic matrices using drug loaded filaments prepared via HME to achieve an in vitro (swelling, erosion and drug release) and in vivo (drug absorption) performance which is analogous to hydrophilic matrix tablets developed through conventional approaches.

Trends in global prescribing of antidiabetic medicines in primary care: A systematic review of literature between 2000-2018.

The aim of this review was to examine changes in the use of diabetes medicines prescribed to treat type 2 diabetes in the primary care setting. Five electronic databases were searched using strict inclusion/exclusion criteria. The quality of eligible studies was appraised using the Newcastle-Ottawa Scale.

Effect of preparation method on the surface properties and UV imaging of indomethacin solid dispersions.

This work explores the use of UV imaging in solid dispersion systems. Solid dispersions are one of the common strategies used in improving the dissolution of poorly soluble drugs. Three manufacturing techniques (spray drying (SD), freeze drying (FD) and homogenising (HG)) are investigated.

Direct imaging of the dissolution of salt forms of a carboxylic acid drug.

The optimisation of the pharmaceutical properties of carboxylic acid drugs is often conducted by salt formation. Often, the salt with the best solubility is not chosen due to other factors such as stability, solubility, dissolution and bioavailability that are taken into consideration during the preformulation stage. This work uses advanced imaging techniques to give insights into the preformulation properties that can aid in the empirical approach often used in industry for the selection of salts.

Cost analysis of type 2 diabetes mellitus treatment in economically developed countries.

Introduction: There is a growing need to evaluate the factors contributing to the increase in health expenditures, as well as the cost of medicines used in the treatment of Type 2 diabetes mellitus (T2DM) in the economically developed countries.

Areas Covered: A systematic searching of studies describing the direct cost of T2DM and medicine cost of treating T2DM. The quality of the studies found eligible for this study were assessed using a methodological quality appraisal tool.